2-甲氧基喹啉-7-羧酸甲酯 | 1451154-40-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 2-甲氧基喹啉-7-羧酸甲酯
• 英文名称: methyl 2-methoxyquinoline-7-carboxylate
• 英文别名: Methyl 2-methoxyquinoline-7-carboxylate
• CAS: 1451154-40-7
• 化学式: C₁₂H₁₁NO₃
• 分子量: 217.224
• InChiKey: GDLOIGJPEGXUMW-UHFFFAOYSA-N

物化性质

• 沸点：
  332.7±22.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-甲氧基喹啉-7-羧酸甲酯 在 1-丙基磷酸酐 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 2’-(tert-butyl)-1-(2-methoxyquinoline-7-carbonyl)-4’,6’-dihydrospiro[piperidine-4,5’-pyrazolo[3,4-c]pyridin]-7’(2’H)-one
  参考文献：
  名称：

  Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

  摘要：

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.

  DOI：

  10.1021/jm401033t
• 作为产物：
  描述：

  喹啉-7-羧酸甲酯 在 过氧乙酸 、 溶剂黄146 、 三乙胺 、 甲基磺酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 36.25h， 生成 2-甲氧基喹啉-7-羧酸甲酯
  参考文献：
  名称：

  Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

  摘要：

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.

  DOI：

  10.1021/jm401033t

文献信息

• Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure
  作者：David A. Griffith、Robert L. Dow、Kim Huard、David J. Edmonds、Scott W. Bagley、Jana Polivkova、Dongxiang Zeng、Carmen N. Garcia-Irizarry、James A. Southers、William Esler、Paul Amor、Kathrine Loomis、Kirk McPherson、Kevin B. Bahnck、Cathy Préville、Tereece Banks、Dianna E. Moore、Alan M. Mathiowetz、Elnaz Menhaji-Klotz、Aaron C. Smith、Shawn D. Doran、David A. Beebe、Matthew F. Dunn

  DOI：10.1021/jm401033t

  日期：2013.9.12

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.